Article | Published:

Pediatrics

In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

International Journal of Obesityvolume 42pages13171325 (2018) | Download Citation

Abstract

Background/objectives

Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy.

Methods

In the prospective Chinese birth cohort “Children of 1997” (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2– < 8 years) and adolescence (8–16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life.

Results

In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (−0.13, 95% confidence interval (CI) −0.22, −0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4).

Conclusions

In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Durnwald C, Landon M. Fetal links to chronic disease: the role of gestational diabetes mellitus. Am J Perinatol. 2012;30:343–346.

  2. 2.

    Tam WH, Ma RC, Yang X, Ko GT, Tong PC, Cockram CS, et al. Glucose intolerance and cardiometabolic risk in children exposed to maternal gestational diabetes mellitus in utero. Pediatrics. 2008;122:1229–1234.

  3. 3.

    Aydin S. The presence of the peptides apelin, ghrelin and nesfatin-1 in the human breast milk, and the lowering of their levels in patients with gestational diabetes mellitus. Peptides. 2010;31:2236–2240.

  4. 4.

    Bouret SG, Simerly RB. Developmental programming of hypothalamic feeding circuits. Clin Genet. 2006;70:295–301.

  5. 5.

    Plagemann A, Harder T, Franke K, Kohlhoff R. Long-term impact of neonatal breast-feeding on body weight and glucose tolerance in children of diabetic mothers. Diabetes Care. 2002;25:16–22.

  6. 6.

    Rodekamp E, Harder T, Kohlhoff R, Franke K, Dudenhausen JW, Plagemann A. Long-term impact of breast-feeding on body weight and glucose tolerance in children of diabetic mothers: role of the late neonatal period and early infancy. Diabetes Care. 2005;28:1457–1462.

  7. 7.

    Crume TL, Ogden L, Maligie M, Sheffield S, Bischoff KJ, McDuffie R, et al. Long-term impact of neonatal breastfeeding on childhood adiposity and fat distribution among children exposed to diabetes in utero Diabetes Care. 2011;34:641–645.

  8. 8.

    Crume TL, Ogden LG, Mayer-Davis EJ, Hamman RF, Norris JM, Bischoff KJ, et al. The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study. Int J Obes (Lond). 2012;36:529–534.

  9. 9.

    Mayer-Davis EJ, Rifas-Shiman SL, Zhou L, Hu FB, Colditz GA, Gillman MW. Breast-feeding and risk for childhood obesity: does maternal diabetes or obesity status matter? Diabetes Care. 2006;29:2231–2237.

  10. 10.

    Brion MJ, Lawlor DA, Matijasevich A, Horta B, Anselmi L, Araujo CL, et al. What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts. Int J Epidemiol. 2011;40:670–680.

  11. 11.

    Schooling CM, Hui LL, Ho LM, Lam TH, Leung GM. Cohort Profile: “Children of 1997”: a Hong Kong Chinese birth cohort. Int J Epidemiol. 2012;41:611–620.

  12. 12.

    Kwok MK, Schooling CM, Lam TH, Leung GM. Does breastfeeding protect against childhood overweight? Hong Kong’s ‘Children of 1997’ birth cohort. Int J Epidemiol. 2010;39:297–305.

  13. 13.

    Plagemann A, Harder T. Fuel-mediated teratogenesis and breastfeeding. Diabetes Care. 2011;34:779–781.

  14. 14.

    Lam TH, Leung GM, Ho LM. The effects of environmental tobacco smoke on health services utilization in the first eighteen months of life. Pediatrics. 2001;107:E91.

  15. 15.

    WHO. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76–85.

  16. 16.

    de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;89:660–667.

  17. 17.

    Karlberg J. A biologically-oriented mathematical model (ICP) for human growth. Acta Paediatr Scand Suppl. 1989;350:70–94.

  18. 18.

    Kwok MK, Leung GM, Lam TH, Schooling CM. Breastfeeding, childhood milk consumption, and onset of puberty. Pediatrics. 2012;130:e631–e639.

  19. 19.

    Kwok MK, Leung GM, Schooling CM. Breast feeding and early adolescent behaviour, self-esteem and depression: Hong Kong’s ‘Children of 1997’ birth cohort. Arch Dis Child. 2013;98:887–894.

  20. 20.

    Kwok MK, Leung GM, Schooling CM. Breastfeeding and adolescent blood pressure: evidence from Hong Kong’s “Children of 1997” Birth Cohort. Am J Epidemiol. 2013;178:928–936.

  21. 21.

    Schafer JL. Multiple imputation: a primer. Stat Methods Med Res. 1999;8:3–15.

  22. 22.

    Moons KG, Donders RA, Stijnen T, Harrell FE Jr. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol. 2006;59:1092–101.

  23. 23.

    Moore TR. Fetal exposure to gestational diabetes contributes to subsequent adult metabolic syndrome. Am J Obstet Gynecol. 2010;202:643–649.

  24. 24.

    Garcia-Vargas L, Addison SS, Nistala R, Kurukulasuriya D, Sowers JR. Gestational diabetes and the offspring: implications in the development of the cardiorenal metabolic syndrome in offspring. Cardiorenal Med. 2012;2:134–142.

  25. 25.

    Tam WH, Ma RC, Yang X, Li AM, Ko GT, Kong AP, et al. Glucose intolerance and cardiometabolic risk in adolescents exposed to maternal gestational diabetes: a 15-year follow-up study. Diabetes Care. 2010;33:1382–1384.

  26. 26.

    Lawlor DA, Fraser A, Lindsay RS, Ness A, Dabelea D, Catalano P, et al. Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort. Diabetologia. 2010;53:89–97.

  27. 27.

    Philipps LH, Santhakumaran S, Gale C, Prior E, Logan KM, Hyde MJ, et al. The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis. Diabetologia. 2011;54:1957–1966.

  28. 28.

    Houde AA, Ruchat SM, Allard C, Baillargeon JP, St-Pierre J, Perron P, et al. LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. Epigenomics. 2015;7:1111–1122.

  29. 29.

    Allard C, Desgagne V, Patenaude J, Lacroix M, Guillemette L, Battista MC, et al. Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns. Epigenetics. 2015;10:342–351.

  30. 30.

    Cote S, Gagne-Ouellet V, Guay SP, Allard C, Houde AA, Perron P, et al. PPARGC1alpha gene DNA methylation variations in human placenta mediate the link between maternal hyperglycemia and leptin levels in newborns. Clin Epigenetics. 2016;8:72.

  31. 31.

    Aydin S, Celik O, Gurates B, Sahin I, Ulas M, Yilmaz M, et al. Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus. Peptides. 2013;49:123–310.

  32. 32.

    Aris IM, Soh SE, Tint MT, Saw SM, Rajadurai VS, Godfrey KM, et al. Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in utero. Eur J Nutr. 2015;56:55–64.

  33. 33.

    Touger L, Looker HC, Krakoff J, Lindsay RS, Cook V, Knowler WC. Early growth in offspring of diabetic mothers. Diabetes Care. 2005;28:585–589.

  34. 34.

    Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care. 1998;21:B142–B149.

  35. 35.

    Aris IM, Soh SE, Tint MT, Saw SM, Rajadurai VS, Godfrey KM, et al. Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population. Am J Clin Nutr. 2015;102:1104–1112.

  36. 36.

    Fenger-Gron J, Fenger-Gron M, Blunck CH, Schonemann-Rigel H, Wielandt HB. Low breastfeeding rates and body mass index in Danish children of women with gestational diabetes mellitus. Int Breastfeed J. 2015;10:26.

  37. 37.

    Owen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics. 2005;115:1367–1377.

  38. 38.

    Owen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence. Am J Clin Nutr. 2006;84:1043–1054.

  39. 39.

    Horta BL, Loret de MC, Victora CG. Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis. Acta Paediatr Suppl. 2015;104:30–37.

  40. 40.

    Pettitt DJ, Forman MR, Hanson RL, Knowler WC, Bennett PH. Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians. Lancet. 1997;350:166–168.

  41. 41.

    Schaefer-Graf UM, Hartmann R, Pawliczak J, Passow D, bou-Dakn M, Vetter K, et al. Association of breast-feeding and early childhood overweight in children from mothers with gestational diabetes mellitus. Diabetes Care. 2006;29:1105–1107.

  42. 42.

    Brion MJ. Commentary: assessing the impact of breastfeeding on child health: where conventional methods alone fall short for reliably establishing causal inference. Int J Epidemiol. 2010;39:306–307.

  43. 43.

    Martin RM, Patel R, Kramer MS, Guthrie L, Vilchuck K, Bogdanovich N, et al. Effects of promoting longer-term and exclusive breastfeeding on adiposity and insulin-like growth factor-I at age 11.5 years: a randomized trial. JAMA. 2013;309:1005–1013.

  44. 44.

    Eriksson JG, Forsen TJ, Osmond C, Barker DJ. Pathways of infant and childhood growth that lead to type 2 diabetes. Diabetes Care. 2003;26:3006–3010.

  45. 45.

    World Health Organisation. Global action plan for the prevention and control of noncommunicable diseases 2013–2020. 2013. Geneva, Switzerland.

  46. 46.

    Bouhours-Nouet N, Dufresne S, de Casson FB, Mathieu E, Douay O, Gatelais F, et al. High birth weight and early postnatal weight gain protect obese children and adolescents from truncal adiposity and insulin resistance: metabolically healthy but obese subjects? Diabetes Care. 2008;31:1031–1036.

Download references

Acknowledgements

We thank colleagues at the Student Health Service and Family Health Service of the Department of Health for their assistance and collaboration. We also thank the late Dr. Connie O for coordinating the project and all the fieldwork for the initial study in 1997–1998. This work is a sub-study of the “Children of 1997” birth cohort which was initially supported by the Health Care and Promotion Fund, Health and Welfare Bureau, Government of the Hong Kong SAR [HCPF Grant # 216106] and re-established in 2005 with support from the Health and Health Services Research Fund [HHSRF Grant # 03040771], and the University Research Committee Strategic Research Theme (SRT) of Public Health, The University of Hong Kong. This sub-study builds on information added to the birth cohort by RFCID grant # 04050172 and HHSRF grant # 08090761, and was funded by the Health and Health Services Research Fund [HHSRF Grant # 12132731], Government of the Hong Kong SAR.

Author contributions

Drs Hui and Schooling developed the study conception, directed the study’s analytic strategy and wrote the manuscript. Drs Li, Nelson, Lee, and Leung contributed to the interpretation of the data and critically revised the paper. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Author information

Affiliations

  1. Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

    • L. L. Hui
    • , A. M. Li
    • , E. A. S. Nelson
    •  & G. M. Leung
  2. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    • L. L. Hui
    •  & C. M. Schooling
  3. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    • S. L. Lee
  4. CUNY Graduate School of Public Health and Health Policy, New York, NY, USA

    • C. M. Schooling

Authors

  1. Search for L. L. Hui in:

  2. Search for A. M. Li in:

  3. Search for E. A. S. Nelson in:

  4. Search for G. M. Leung in:

  5. Search for S. L. Lee in:

  6. Search for C. M. Schooling in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to C. M. Schooling.

Electronic supplementary material

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41366-018-0077-2